Diterpenoids from caribbean gorgonians act as noncompetitive inhibitors of the nicotinic acetylcholine receptor |
| |
| Authors: | Vesna A Eterović Richard M Hann P A Ferchmin Abimael D Rodriguez Lian Li Yung-Hui Lee Mark G McNamee |
| |
| Institution: | 1. Department of Biochemistry and Center for Molecular and Behavioural Neuroscience, School of Medicine, Universidad Central del Caribe, 00960, Bayamón, Puerto Rico, USA
3. Department of Chemistry, University of Puerto Rico, Rio Piedras, 00931, Puerto Rico, USA
4. Department of Biochemistry and Biophysics, University of California, 95616, Davis, California, USA
|
| |
| Abstract: | | 1. |
Three cyclic diterpenoids isolated from gorgonians of theEunicea genus and characterized as eupalmerin acetate (EUAC), 12,13-bisepieupalmerin (BEEP), and eunicin (EUNI) were found to be pharmacologically active on the nicotinic acetylcholine receptor (AChR).
| | 2. |
The receptor from the BC3H-1 muscle cell line was expressed inXenopus laevis oocytes and studied with a two-electrode voltage clamp apparatus.
| | 3. |
All three compounds reversibly inhibited ACh-induced currents, with IC50's from 6 to 35µM. ACh dose-response curves suggested that his inhibition was noncompetitive. The cembranoids also increased the rate of receptor desensitization.
| | 4. |
Radioligand-binding studies using AChR-rich membranes fromTorpedo electric organ indicated that all three cembranoids inhibited high-affinity 3H]phencyclidine binding, with IC50's of 0.8, 11.6, and 63.8µM for EUNI, EUAC, and BEEP, respectively. The cembranoids at a 100µM concentration did not inhibit  -125I]bungarotoxin binding to either membrane-bound or solubilized AChR.
| | 5. |
It is concluded that these compounds act as noncompetitive inhibitors of peripheral AChR.
|
|
| |
| Keywords: | nicotinic acetylcholine receptor cembranoids noncompetitive inhibitors eupalmerin acetate 12 13-bisepieupalmerin eunicin |
| 本文献已被 SpringerLink 等数据库收录！ |
|
